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Rheumatoid ArthritisPhase 4VEDERANCT02433184

Very Early Versus Delayed Etanercept in Patients With RA

A Phase 4 study testing Etanercept, Methotrexate and Sulfasalazine in people with Rheumatoid Arthritis, run by University of Leeds at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The main aim of the study is to determine whether TNFi instituted as first-line therapy in early RA confers better outcomes (clinical, structural and immunological) compared to delayed TNFi start; implying particular dominance of TNF in early disease, a changing role of TNF with disease duration and hence… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Etanercept, Methotrexate and Sulfasalazine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteUnited Kingdom
Study dates
Jul 2011to Jul 2019
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female patients aged between 18 and 80 years.
  • Diagnosis of rheumatoid arthritis (new 2010 ACR/EULAR RA classification criteria).
  • Symptom onset within the preceding 12 months.
  • Patients with active RA at baseline: clinical evidence of synovitis (or imaging evidence of synovitis in cases of uncertainty/subclinical disease) in hand and/or wrist joints evaluable by ultrasound and MRI, and DAS28-ESR>3.2.
  • Seropositivity for anti-citrullinated peptide antibody (ACPA) and/or rheumatoid factor. If ACPA and rheumatoid factor are both negative, presence of power Doppler in at least 1 joint on ultrasound imaging.
  • DMARD-naive (with the exception of previous exposure to hydroxychloroquine for an indication other than RA).
  • All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives.

Who cannot join

  • Previous treatment with DMARDs for the management of RA.
  • Intramuscular or intra-articular (of non-target joint) corticosteroid within 28 days of the screening visit; intra-articular steroid of the chosen target joint within 12 weeks of screening.
  • Oral steroid of greater than 10mg prednisolone daily, or change in oral steroid dose within 28 days of study drug initiation at the baseline visit.
  • Use (including use as required) of more than one NSAID, change in NSAID or change in dose of NSAID within 28 days of the baseline visit.
  • Contraindications to MRI (e.g. pacemaker) or unable or unwilling to attend for all imaging assessments. In patients with previous penetrating trauma to the eye, or patients at high risk of previous metal foreign body injury to the eye (e.g. welding), skull x-ray will be performed; these patients may be included in the absence of residual metal fragments on x-ray.
  • Pregnancy or breastfeeding.
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  • Other contraindications to TNFi as determined by local prescribing guidelines and physician discretion, including:
  • Active infection, open leg ulcers, previously infected prosthetic joint (unless completely removed), septic arthritis in last year, HIV, Hepatitis B or Hepatitis C carriers, previous malignancy within 10 years (except basal cell carcinoma), severe heart failure (New York Heart Association grade 3 or more), any history of demyelinating disease, uncontrolled diabetes, pulmonary fibrosis, bronchiectasis, previous PUVA therapy (of >1000 Joules), history of TB or evidence of latent TB on chest x-ray/TB testing (in the latter event, a patient may be included if treated with isoniazid and pyridoxine one month before starting the study and for a further 6 months whilst on study treatments).
  • History of other significant medical conditions, including:
  • Severe pulmonary disease, defined as requiring previous hospital admission or supplemental oxygen.
  • Active or severe cardiovascular disease: uncontrolled hypertension, myocardial infarction within 12 months of screening, unstable angina within 6 months of screening.
  • Other immunodeficiency disorders.
  • Connective tissue diseases, e.g. primary Sjogren's syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis.
  • Psoriasis.
  • Renal impairment (creatinine ≥ 175µmol/L).
  • Blood disorders: neutropenia (neutrophils < 2.0 x 109/L), thrombocytopenia (platelets < 125 x 109/L), or anaemia (haemoglobin < 8 g/dL).
  • Abnormal liver function (alanine transaminase, ALT > 3 x upper limit of normal).
  • Planned surgery within the study period which is expected to require omission of any study medication of 28 days or more.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Institute of Rheumatic & Musculoskeletal Medicine, Chapel Allerton Hospital

    Leeds, West Yorkshire, LS7 4SA

Other trials in United Kingdom

About this study

Official title: A Prospective, Single-centre, Randomised Study Evaluating the Clinical, Imaging and Immunological Depth of Remission Achieved by Very Early Versus Delayed Etanercept in Patients With Rheumatoid Arthritis

The main aim of the study is to determine whether TNFi instituted as first-line therapy in early RA confers better outcomes (clinical, structural and immunological) compared to delayed TNFi start; implying particular dominance of TNF in early disease, a changing role of TNF with disease duration and hence, confirmation of a biological window of opportunity.

Being tested
Etanercept, Methotrexate, Sulfasalazine, Hydroxychloroquine
Keywords
Etanercept, treat to target, Disease Modifying Antirheumatic Drugs (DMARDs)
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtanerceptDrug

    Etanercept will be administered subcutaneously at a dose of 50 mg weekly and will be discontinued at the primary endpoint (48 weeks).

  • MethotrexateDrug

    Methotrexate will be administered orally at a starting dose of 15 mg and will be increased to 25mg weekly at 2 weeks.

  • SulfasalazineDrug

    Sulfasalazine will be added at weeks 8,12,16 or 20 if the subject fails to achieve low disease activity, administered orally at a dose of 1g twice daily. Will be discontinued if starting etanercept at 24 weeks.

  • HydroxychloroquineDrug

    Hydroxychloroquine will be added at weeks 8,12,16 or 20 if the subject fails to achieve low disease activity, administered at a dose of 200mg daily. Will be discontinued if starting etanercept at 24 weeks.

  • EtanerceptDrug

    Etanercept will be added at 24 weeks, if a subject fails to achieve clinical remission,at a dose of 50 mg weekly and will be discontinued at 48 weeks with the exception of those patients who are eligible to continue according to local prescribing guidelines (NICE guidelines)

  • MethotrexateDrug

    Methotrexate will be administered orally at a starting dose of 15 mg weekly, increasing to 20mg and 25mg weekly at weeks 4 and 8 respectively.

Study groups in NCT02433184
Study groupRoleWhat they receive
EtanerceptExperimentalTreatment Arm 1 will receive etanercept and methotrexate combination therapy administered for a total duration of 48 weeks.
Receives: Drug: Etanercept; Drug: Methotrexate
Methotrexate-treat to targetActive comparatorTreatment Arm 2 will receive initial methotrexate monotherapy with adoption of a treat to target protocol (standard care involving monthly DAS28-ESR assessment with escalation to combination sDMARD therapy if not achieving LDA at, or after, 8 weeks) and step-up to etanercept and methotrexate at 24 weeks if failing to achieve clinical remission
Receives: Drug: Methotrexate; Drug: Sulfasalazine; Drug: Hydroxychloroquine; Drug: Etanercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical remission

    Proportion of patients that achieve clinical remission (Disease activity Score, DAS28 <2.6) at 48 weeks, following either treatment strategy.

    Measured: 48 weeks

Secondary outcomes (12)

  1. Change in MRI synovitis

    Change in MRI synovitis between baseline and 48 weeks.

    Measured: baseline and week 48

  2. CDAI (clinical disease activity index)

    Change in CDAI score from baseline at weeks 12, 24, 48 and 96

    Measured: weeks 12, 24, 48 and 96

  3. SDAI (simplified disease activity index)

    Change in SDAI score from baseline at weeks 12, 24, 36 \& 48.

    Measured: weeks 12, 24, 48 and 96

  4. ACR(American College of Rheumatology) response scores

    ACR response score from baseline at weeks 12, 24, 48 and 96

    Measured: weeks 12, 24, 48 and 96

  5. EULAR(European League Against Rheumatism)response criteria

    EULAR response score from baseline

    Measured: weeks 12, 24, 48 and 96

  6. Physical function, assessed by HAQ(health assessment questionnaire)

    Measured: weeks 12, 24, 48 and 96

  7. Quality of life scores assessed by RA-QoL(RA quality of life questionnaire)

    Measured: weeks 12, 24, 48 and 96

  8. Work instability, assessed by RA-WIS(RA work instability questionnaire)

    Measured: weeks 12, 24, 48 and 96

  9. HRUS (High Resolution Ultrasound)

    Change in HRUS from baseline

    Measured: weeks 0, 12, 24 and 48

  10. Radiographic scores

    Change in joint damage assessed by modified Sharp score.

    Measured: weeks 48 and 96

  11. Immunological parameters in blood sample

    Change in immunological markers of inflammation between baseline and weeks 12, 24 and 48.

    Measured: weeks 0, 12, 24 and 48

  12. Immunological parameters in synovial tissue

    Change in immunological markers of inflammation between baseline and weeks 24 and 48.

    Measured: weeks 0, 24, +/- 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2015 (estimated)
  2. Study startJul 2011
  3. Primary completionAug 2017
  4. Study completionJul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02433184
Sponsor's protocol ID
RR10/9592
Acronym
VEDERA
Status last verified
Sep 2019
First submitted
23 Apr 2015
Last updated
9 Sep 2019
Results posted
No
Data monitoring committee
No

Publications

  • Anioke IC, Tastekin F, Alp G, Ng H, Ravi P, Parker I, Lou M, Gul H, Duquenne L, Villeneuve E, Nam JL, Sharrack S, Buch MH, Conaghan PG, Mankia K, Emery P, Ponchel F. T-cell subset biomarkers across the rheumatoid arthritis disease continuum: from clinical utility to adoption in daily practice. Rheumatology (Oxford). 2026 Jun 3;65(6):keag286. doi: 10.1093/rheumatology/keag286.

    PubMed 42271628

  • Emery P, Horton S, Dumitru RB, Naraghi K, van der Heijde D, Wakefield RJ, Hensor EMA, Buch MH. Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with delayed etanercept in RA: the VEDERA trial. Ann Rheum Dis. 2020 Apr;79(4):464-471. doi: 10.1136/annrheumdis-2019-216539. Epub 2020 Jan 29.

    PubMed 31996367

  • Dumitru RB, Horton S, Hodgson R, Wakefield RJ, Hensor EMA, Emery P, Buch MH. A prospective, single-centre, randomised study evaluating the clinical, imaging and immunological depth of remission achieved by very early versus delayed Etanercept in patients with Rheumatoid Arthritis (VEDERA). BMC Musculoskelet Disord. 2016 Feb 5;17:61. doi: 10.1186/s12891-016-0915-0.

    PubMed 26847108

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Etanercept, Methotrexate and Sulfasalazine in people with Rheumatoid Arthritis, run by University of Leeds at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical remission (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02433184, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2019.

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